Nastoupil LJ, Jain MD, Feng L, Spiegel JY, Ghobadi A, Lin Y, Dahiya S, Lunning M, Lekakis L, Reagan P et al (2020) Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US Lymphoma CAR T Consortium. J Clin Oncol 38(27):3119–3128

Article  PubMed  PubMed Central  Google Scholar 

Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF, Xu J, Zhuang Y, Zhang W, Weng XQ et al (2019) Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci U S A 116(19):9543–9551

Article  PubMed  PubMed Central  CAS  Google Scholar 

Singh N, Orlando E, Xu J, Xu J, Binder Z, Collins MA, O’Rourke DM, Melenhorst JJ (2020) Mechanisms of resistance to CAR T cell therapies. Semin Cancer Biol 65:91–98

Article  PubMed  CAS  Google Scholar 

Susanibar Adaniya SP, Cohen AD, Garfall AL (2019) Chimeric antigen receptor T cell immunotherapy for multiple myeloma: a review of current data and potential clinical applications. Am J Hematol 94(S1):S28–S33

Article  PubMed  CAS  Google Scholar 

Aplenc R, Meshinchi S, Sung L, Alonzo T, Choi J, Fisher B, Gerbing R, Hirsch B, Horton T, Kahwash S et al (2020) Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children’s Oncology Group. Haematologica 105(7):1879–1886

Article  PubMed  PubMed Central  Google Scholar 

Pritchard CC, Smith C, Salipante SJ, Lee MK, Thornton AM, Nord AS, Gulden C, Kupfer SS, Swisher EM, Bennett RL et al (2012) ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 14(4):357–366

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pritchard CC, Salipante SJ, Koehler K, Smith C, Scroggins S, Wood B, Wu D, Lee MK, Dintzis S, Adey A et al (2014) Validation and implementation of targeted capture and sequencing for the detection of actionable mutation, copy number variation, and gene rearrangement in clinical cancer specimens. J Mol Diagn 16(1):56–67

Article  PubMed  PubMed Central  CAS  Google Scholar 

Song MK, Park BB, Uhm JE (2019) Resistance mechanisms to CAR T-cell therapy and overcoming strategy in B-cell hematologic malignancies. Int J Mol Sci 20(20):5010

Article  PubMed  PubMed Central  CAS  Google Scholar 

Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y et al (2017) Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377(26):2531–2544

Article  PubMed  PubMed Central  CAS  Google Scholar 

Oak J, Spiegel JY, Sahaf B, Natkunam Y, Long SR, Hossain N, Mackall CL, Kong KA, Miklos DB (2018) Target antigen downregulation and other mechanisms of failure after axicabtagene ciloleucel (CAR19) therapy. Blood 132(Supplement 1):4656

Article  Google Scholar 

Zhou X, Rasche L, Kortum KM, Mersi J, Einsele H (2023) BCMA loss in the epoch of novel immunotherapy for multiple myeloma: from biology to clinical practice. Haematologica 108(4):958–968

Article  PubMed  CAS  Google Scholar 

Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, Vogl DT, Weiss BM, Dengel K, Nelson A et al (2019) B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest 129(6):2210–2221

Article  PubMed  PubMed Central  Google Scholar 

Majzner RG, Mackall CL (2018) Tumor antigen escape from CAR T-cell therapy. Cancer Discov 8(10):1219–1226

Article  PubMed  CAS  Google Scholar 

Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M et al (2018) Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med 24(10):1504–1506

Article  PubMed  CAS  Google Scholar 

Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR et al (2015) Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov 5(12):1282–1295

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ledererova A, Dostalova L, Kozlova V, Peschelova H, Ladungova A, Culen M, Loja T, Verner J, Pospisilova S, Smida M et al (2021) Hypermethylation of CD19 promoter enables antigen-negative escape to CART-19 in vivo and in vitro. J Immunother Cancer 9(8):e002352

Article  PubMed  PubMed Central  Google Scholar 

Braig F, Brandt A, Goebeler M, Tony HP, Kurze AK, Nollau P, Bumm T, Bottcher S, Bargou RC, Binder M (2017) Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood 129(1):100–104

Article  PubMed  CAS  Google Scholar 

Da Via MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterjee M et al (2021) Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med 27(4):616–619

Article  PubMed  Google Scholar 

Leblay N, Maity R, Barakat E, McCulloch S, Duggan P, Jimenez-Zepeda V, Bahlis NJ, Neri P (2020) Cite-Seq profiling of T cells in multiple myeloma patients undergoing BCMA targeting CAR-T or bites immunotherapy. Blood 136(1):11–12

Article  Google Scholar 

Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai YT, Prabhala R, Alonso A, Sperling AS, Campbell T, Petrocca F et al (2021) Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun 12(1):868

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fischer J, Paret C, El Malki K, Alt F, Wingerter A, Neu MA, Kron B, Russo A, Lehmann N, Roth L et al (2017) CD19 isoforms enabling resistance to CART-19 immunotherapy are expressed in B-ALL patients at initial diagnosis. J Immunother 40(5):187–195

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yu H, Sotillo E, Harrington C, Wertheim G, Paessler M, Maude SL, Rheingold SR, Grupp SA, Thomas-Tikhonenko A, Pillai V (2017) Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma. Am J Hematol 92(1):E11–E13

Article  PubMed  CAS  Google Scholar 

Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES et al (2018) Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica 103(5):e215–e218

Article  PubMed  PubMed Central  CAS  Google Scholar 

Hamieh M, Dobrin A, Cabriolu A, van der Stegen SJC, Giavridis T, Mansilla-Soto J, Eyquem J, Zhao Z, Whitlock BM, Miele MM et al (2019) CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature 568(7750):112–116

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ruella M, Xu J, Barrett DM, Fraietta JA, Reich TJ, Ambrose DE, Klichinsky M, Shestova O, Patel PR, Kulikovskaya I et al (2018) Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med 24(10):1499–1503

Article  PubMed  PubMed Central  CAS  Google Scholar 

Laurent C, Syrykh C, Hamon M, Adelaide J, Guille A, Escudie F, Jalowicki G, Fina F, Bardet A, Mescam L et al (2022) Resistance of B-cell lymphomas to CAR T-cell therapy is associated with genomic tumor changes which can result in transdifferentiation. Am J Surg Pathol 46(6):742–753

Article  PubMed  Google Scholar 

Gauto-Mariotti E, Nguyen AJ, Waters C, Scurti GM, Haddad S, Velankar MM, Dalheim AV, Dronzek V, Ketterling RP, Nishimura MI et al (2022) Transdifferentiation of high-grade B-cell lymphoma with MYC and BCL2 rearrangements into histiocytic sarcoma after CAR T-cell therapy: a case report. J Hematop 15(4):229–237

Article  Google Scholar